PGS Exclusive: How the FDA Shapes Modern Science, including Cancer Therapeutics by Daniel Carpenter

Science is often portrayed as an independent activity, a calling that involves the isolation of the ivory tower and the lab. Yet in ways that we scarcely recognize, almost every facet of modern medical science is deeply shaped by the government, and in particular by the U.S. Food and Drug Administration (FDA). The very structure, procedure, methods and concepts of modern medical science – as well as the way that billions of dollars are spent – are deeply shaped by the FDA, in ways illuminated by a new Princeton book, Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA, written by Harvard professor Daniel Carpenter. Here, Carpenter reflects on how the FDA shapes modern science, specifically focusing on cancer therapeutics.

Journalists report daily on the latest results from a “Phase II” trial or a “Phase III” experiment. Yet where do these terms come from? When did we demand that medical experiments be partitioned into phases? For better or worse, these phases created the modern clinical trial industry, and they are the legacy of the FDA. Whenever scientists begin work on a drug or medical device, they must submit an experimental “protocol” that specifies what will happen not just in the next experiment, but the one after that, and the one after that. The very concepts and statistical measures used in these experiments must be approved by the FDA before any of the tests can begin. The entire world – ranging from European drug regulators and the World Health Organization to agencies and researchers in China, India, Israel and Latin America – now relies upon this phased system of experiment. But until now, no one has recognized it for what it is: the creation of an American government agency.

In terms of developing new treatments, cancer therapeutics has arguably been one of the success stories of modern medical science. Drugs like cisplatin and paclitaxel have become reliable weapons in the oncologist’s arsenal, and they have been infused into the veins of tens of millions of human beings. Yet the very terms of modern oncology – what counts as a success when treating cancer, such as tumor progression and viral load – have been shaped by what the FDA accepts as “surrogate endpoints” for a clinical trial. When the FDA decided that tumor regression counts as evidence of treatment efficacy for cancer patients, drug companies, scientists and statisticians around the world responded by tailoring their experiments, measures and statistical methods to the standard of tumor regression. The very shape of oncology was changed.

Historian of science Steven Shapin has described scientists as “struggling for credibility and authority,” and the FDA is also moved and constrained by a similar politics of legitimacy and trust. The agency’s vast power is enabled, but also limited by, its reputation. And because science and medicine rarely speak with one voice – cardiologists disagree with endocrinologists on the proper course of diabetes treatment, statisticians dissent from physicians on whether an experiment is informative or rigorous – the politics of pharmaceutical regulation depends upon a delicate equipoise among constituencies and audiences. The conflict between oncologists and FDA officials changed both the course of cancer treatment as well as the operations of regulators.

Does the FDA’s influence upon science help or hinder medical progress? This is a complicated question to which pundits and politicians have given simplistic answers. Yet talk to a scientist in the medical or biotechnology field, and they will tell you that theirs is a heavily regulated life. Any experiment with humans or animals needs to have a protocol designed in advance of the tests, needs approval by an organizational board or two (including a separate committee if human subjects are involved), is subject to inspection by federal agencies at any time, and must spell out the sequence of tests and methods used. And if the experiment involves a drug or device (and now, a tobacco product) the experiment needs assent of the U.S. Food and Drug Administration (FDA).

New historical and statistical evidence shows us that FDA decisions can scare off drug development by inducing companies and scientists to abandon their therapeutic projects. The politics of reputation can work to ameliorate or exacerbate these constraints. Some politicians, companies and disease sufferers press the agency for more rapid approval? of new therapies, while consumer advocates, other politicians and many medical professionals press the agency toward more stringent requirements upon drugs and drug experiments. In other ways, by standardizing terms and expectations, FDA regulations make scientific progress more possible. When statistical tests and physiologic measures are standardized; when scientists speak to one another with a common vocabulary that has been honed by these standards; when expectations and scientific discourse are focused upon a common protocol for a sequence of experiments – when these things happen, the basic terms of inquiry are stabilized so that effort and thought can be devoted to testing hypotheses and developing treatments. In many cases, regulation permits science to progress.